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Interleukin\u201015 (IL\u201015) activates cytotoxic lymphocytes but is limited by rapid clearance and poor tumor retention. Here, we developed an oncolytic adenovirus encoding IL15C\u2010CBD, an immunocytokine comprising an IL\u201015\/IL\u201015R\u03b1 sushi\u2010domain complex fused to a collagen\u2010binding domain, thereby establishing a self\u2010reinforcing immunostimulatory milieu within tumors. Intratumoral administered OV\u2010IL15C\u2010CBD lyses tumor cells and secretes IL15C\u2010CBD that anchors to extracellular matrix collagens, forming a localized cytokine reservoir. In the murine 4T1 TNBC model, this strategy profoundly remodeled the microenvironment by recruiting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and natural killer cells, depleting regulatory T cells, and polarizing macrophages. toward an M1\u2010like phenotype. Consequently, OV\u2010IL15C\u2010CBD induced significant tumor regression and extended survival without evident systemic toxicity. This therapeutic advantage was further validated in the EMT6 breast tumor model, yielding consistent antitumor efficacy and prolonged survival. Collectively, anchoring immunocytokines to the tumor stroma via oncolytic viruses provides a potentially safe and effective localized immunotherapy for TNBC.\n                  <\/jats:p>","DOI":"10.1002\/advs.77691","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:01:35Z","timestamp":1789563695000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Collagen\u2010Binding IL\u201015 Immunocytokine Armed Oncolytic Adenovirus Establishes a Self\u2010Reinforcing Immunostimulatory Milieu to Potentiate Antitumor Immunity"],"prefix":"10.1002","author":[{"given":"Yaqi","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/NHC\/CAMS School of Basic Medical Sciences Department of Pharmacy Shanghai Institute of Infectious Disease and Biosecurity Shanghai Pudong Hospital Fudan University  Shanghai 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